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46,XX sex reversal 2 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

46,XX sex reversal 2

MONDO:0010218

Also known as:46,XX Sex reversal type 246XX sex reversal 2SRXX2

Overview

GeneticsAutosomal dominant · SOX9 (chr 17)

ResearchLimited published research (6 articles)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Elevated circulating luteinizing hormone level, Decreased serum testosterone concentration, Non-obstructive azoospermia, and Sex reversal and others; and sometimes findings: Ovotestis. 16 total HPO annotations.

Organ System	Phenotype Count	Example Features
Lab test results	2	Elevated circulating luteinizing hormone level, Elevated circulating follicle stimulating hormone level

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

SOX9 function has not been fully characterized.

46,XX sex reversal 2 is associated with mutations in the SOX9 gene on chromosome 17.

GeneReviews

Penetrance

Heterozygous pathogenic variants in NR5A1 that lead to the predicted protein change demonstrated reduced penetrance in 46,XX individuals, with fertile XX phenotypic females described .

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No consensus clinical diagnostic criteria for nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) have been published. However, algorithms have been developed for the evaluation and diagnosis of DSD, including nonsyndromic 46,XX testicular DSD .

Suggestive Findings

Nonsyndromic 46,XX testicular DSD should be considered in individuals with the following clinical, supportive laboratory, and imaging findings.

Clinical findings

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for 46,XX sex reversal 2. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) have been published. Evaluations Following Initial Diagnosis To establish the extent of the condition and needs in an individual diagnosed with nonsyndromic 46,XX testicular DSD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 7. Recommended Surveillance for Individuals with Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development

System/Concern

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for 46,XX sex reversal 2.

6 publications have been identified in PubMed for 46,XX sex reversal 2. Research spans Case Report / Case Series (50%), Basic Science / Preclinical (33%), and Epidemiology / Natural History (17%).

Recent Publications

Tenorio-Castano J (2026). [PMID: 41574449](https://pubmed.ncbi.nlm.nih.gov/41574449/). *Clinical genetics*. [Basic Science / Preclinical]
Zhang X (2026). [PMID: 41508122](https://pubmed.ncbi.nlm.nih.gov/41508122/). *European journal of medical research*. [Case Report / Case Series]
Atasay R (2025). [PMID: 40475171](https://pubmed.ncbi.nlm.nih.gov/40475171/). *Molecular syndromology*. [Basic Science / Preclinical]
Ruggero A (2025). [PMID: 40946339](https://pubmed.ncbi.nlm.nih.gov/40946339/). *Journal of the Association of Genetic Technologists*. [Case Report / Case Series]
Brewer CJ (2024). [PMID: 39530251](https://pubmed.ncbi.nlm.nih.gov/39530251/). *Molecular genetics & genomic medicine*. [Case Report / Case Series]

Data assembled from 6 of 12 sources · Last updated Sep 20, 2026, 5:32 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:278850

GARD

Genetic and Rare Diseases Info Center

GARD:15249

Questions for Your Care Team

→Should I pursue genetic testing for SOX9, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

System/Concern	Evaluation	Comment
Constitutional	Measurement of length/height	To assess for short stature
Endocrinology	Measurement of LH, FSH, total testosterone levels	In those age 10 yrs Assessment of libido, energy, erectile function, acne, breast tenderness, presence of gynecomastia
Urology	Physical exam for evidence of undervirilization	Incl assessment of length width of phallus; location of urethral meatus; location of gonads through palpation size measurement w/orchidometer Digital rectal exam measurement of PSA1
Psychology	Assessment of mood gender identity	By mental health professional Genetic
counseling	By genetics professionals2	To inform affected persons their families re nature, MOI, implications of nonsyndromic 46,XX testicular DSD to facilitate medical personal decision making Individual family support/ resources
Treatment of Manifestations in Individuals with Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development Manifestation/Concern	Treatment	Considerations/Other
Short stature	Growth hormone therapy may be considered.	Referral to endocrinologist recommended Low or absent serum testosterone levels1
Gynecomastia	Reduction mammoplasty may be considered if gynecomastia is causing psychological distress.	Regression of gynecomastia may occur w/testosterone replacement therapy.
Osteopenia	Standard treatment per endocrinologist	May incl calcium, exercise, vitamin D, biphosphonates, or calcitonin
Undervirilization	Standard therapy per urologist	May incl orchidopexy /or hypospadias repair Psychological
distress	Referral to mental health professional	Sensitivity is necessary when conveying information to persons w/nonsyndromic 46,XX testicular DSD about genetic cause of the disorder assoc sterility.

Latest News & Developments

1 recent

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AI-curated news mentioning 46,XX sex reversal 2

Updated Aug 25, 2026

Gene & Cell Therapy•

Pipeline & Approvals

•26 days ago(Aug 25)

First Gene Therapy Approved for Glycogen Storage Disease Type la - Endocrinology Advisor

The FDA approved Genglycos (pariglasgene brecaparvovec-opnr) to reduce daily cornstarch intake in patients aged 8 years and older with glycogen storage disease type Ia. Known as Von Gierke disease, GSDIa is a rare metabolic disorder caused by a mutation in the G6PC gene. This genetic variation leads to a deficiency in glucose-6-phosphatase (G6Pase), an enzyme needed to release glucose into the bloodstream. Without this enzyme, the body cannot properly maintain blood glucose levels, causing severe hypoglycemia and other serious metabolic complications · Pariglasgene brecaparvovec is an adeno-associated virus (AAV) serotype 8 based gene therapy that delivers a functional copy of the G6PC gene into liver cells, enabling the production of normally functioning G6Pase. Ultragenyx stated that as part of its postmarketing commitments to the FDA, the Company will provide 2 years of clinical data from open-label commercial treatment of 50 patients and 20 control patients through its existing GSDIa Disease Monitoring Program. ... Ultragenyx announces US FDA approval of Genglycos™ gene therapy, the first-ever FDA-approved treatment designed to treat the underlying cause of glycogen storage disease type Ia (GSDIa). “The reduced reliance on cornstarch, experienced by patients in our clinical studies, demonstrates this gene therapy’s ability to establish the normal breakdown of glycogen to produce glucose during fasting or episodes of metabolic stress. This ability to regulate glucose has alleviated the disease burden and has the potential to mitigate the risk of severe or life-threatening hypoglycemia for these patients.” Close more info about First Gene Therapy Approved for Glycogen Storage Disease Type la

View all news for 46,XX sex reversal 2

Kisho

46,XX sex reversal 2

Overview

Clinical Presentation

Genetic Landscape

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Latest News & Developments

First Gene Therapy Approved for Glycogen Storage Disease Type la - Endocrinology Advisor

46,XX sex reversal 2

Overview

Clinical Presentation

Genetic Landscape

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Latest News & Developments

First Gene Therapy Approved for Glycogen Storage Disease Type la - Endocrinology Advisor